Silencing of the cellular prion protein (PrPC), by interference RNA (siRNA), reduces HSV-1 and HSV-2 infection in SK-SY5Y cells

The transmissible spongiform encephalopathies (TSEs) are neurodegenerative and fatal diseases, affecting humans and some other animal species. The most accepted hypothesis suggests that the infectious agent, named "prion", is composed mainly by the prion protein scrapie (PrPSc) and it corresponds to an abnormal conformation of a host encoded protein, the cellular prion protein (PrPC), which function is still unknown. However, the ubiquitous expression of PrPC and its highly conserved presence among different species suggests it has a very important role in cell functions. In this work, the PrPC in different cell types, including a primary fish cell culture (Oreochromis spp.), was detected. In addition, based on the human PrPC sequence, we designed a short interfering RNA (siRNA) to silence the PRNP gen in neuronal SK-SY5Y cells. The designed siRNA inhibited the PrPC expression along 96 hours post-transfection and the silenced cells were less susceptible to HSV-1 and HSV-2 infections, in comparison to non siRNA-transfected cells.